The interaction of oligonucleotides, including the codon triplet, drugs, and metal ions to yeast tRNAphe are being investigated by single crystal x-ray crystallographic techniques. Our initial studies have revealed that UUU, UUC and Zn ions bind to the tRNA, and seemingly produce some noticeable conformational changes. Details of these conformational changes and the interaction of a variety of other metals and drugs are in process.